FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896518745> ?p ?o ?g. }

• W2896518745 endingPage "6128" @default.
• W2896518745 startingPage "6127" @default.
• W2896518745 abstract "The paraventricular nucleus of the hypothalamus (PVN) is a centre of the brain that has a number of very intriguing roles in physiology. Alongside its role in neuroendocrine release, body water status and salt/food appetite, to highlight only a few, the PVN has long been appreciated to be a strong influencer of blood pressure control (Carmichael & Wainford, 2015). In particular, the PVN has direct control on sympathetic tone and thereby influences blood pressure through modulating renal function, vasomotor tone and cardiac function. A very general characterization of the population of PVN neurons that contribute to this control is a subset of neurons that are excited in response to glutamate and increase sympathetic tone and blood pressure, and neurons that are inhibited by GABA and decrease sympathetic tone and blood pressure. These signalling pathways are modulated by a wide variety of stimuli and factors (Ferguson et al. 2008), and aberrant PVN signalling and function have been shown to play a role in many diseases with an autonomic component including hypertension (Carmichael & Wainford, 2015) and chronic heart failure (Patel & Zheng, 2012). One major limitation in our current understanding of the role of PVN neurons in blood pressure control has been that most investigations into its roles have been accomplished in anaesthetized or ex vivo approaches. In this issue of The Journal of Physiology, authors Basting et al. (2018) describe a series of experiments focused on demonstrating the necessity and sufficiency of glutamatergic neurons in the PVN towards sympathetically mediated control of blood pressure in conscious mice both in normal physiological function and in a model of neurogenic hypertension (Fig. 1). Utilizing the cutting-edge technical approach of optogenetic stimulation, the authors selectively expressed channelrhodopsin in glutamatergic neurons. This allowed the authors to selectively activate this subpopulation of PVN neurons and observe frequency-dependent increases in blood pressure following stimulation in conscious mice, and demonstrated the sufficiency of glutamatergic PVN neurons towards increasing blood pressure, purportedly through increases in sympathetic tone. Next the authors targeted the necessity of glutamatergic PVN neurons in mediating increased blood pressure in a model of neurogenic hypertension, the deoxycorticosterone acetate (DOCA)–salt model. Here the authors were successfully able to attenuate the increase in pressure from DOCA–salt treatment by selective lesioning of glutamatergic PVN neurons. Taken together these two approaches, one a gain-of-function and the other a loss-of-function, are important evidence for the integral role of glutamatergic PVN neurons in blood pressure control. The lesioning studies also are of interest due to what the authors observed in the non-DOCA–salt controls. They observed a robust blunting of the baroreflex following lesioning along with an increase in glutamate receptor 1 (GluR1) expression in the RVLM and increased urinary noradrenaline excretion. This indicates, as the authors discuss, a potential sympatho-excitation mediated by the RVLM in compensation for lesioning or as a result of dramatic baroreflex dysfunction. In one respect this further defines the integral role of the PVN in mediating baroreflex pathways, but does somewhat complicate the supposed sympatho-inhibitory effects of lesioning. That such robust effects were observed with only an approximately 40% reduction in PVN glutamatergic neurons also supports the suggestion that these neurons can play a major role in mediating sympathetic tone and baroreflex control. These technical approaches are exciting for a number of reasons. First of these is that the authors have now demonstrated the ability to manipulate PVN neurons and observe effects in conscious animals. I look forward with great anticipation to how the laboratory of Dr Lazartigues and others plan to utilize this approach in future investigations. With much attention recently being given to circadian regulation of sympathetic tone and blood pressure control, I am intrigued by the possibilities of this preparation for exploring the role of the PVN in circadian physiology. The PVN receives many projections from the suprachiasmatic nucleus, the ‘master regulator’ of the central clock, and also has a very robust expression of circadian clock genes (Chun et al. 2015). This likely contributes to the rodents’ nocturnal rise in sympathetic tone and blood pressure that corresponds with activity. However, no studies to my knowledge have yet clarified the functional role of PVN activity towards control of diurnal blood pressure rhythms. Could optogenetic stimulation of PVN neurons at times when they are normally relatively quiescent (such as during the early light cycle of nocturnally active mice) be able to entrain sympathetic tone, blood pressure and/or neuroendocrine release to ‘abnormal’ rhythms? Does lesioning of this population of neurons result in a non-dipping phenotype of blood pressure? The possibilities for future work in this area utilizing these approaches is very promising. Although the authors focused on the role of this population of PVN neurons in the model of DOCA–salt hypertension in this current study, it will be of great importance to the field to utilize similar techniques in other models of autonomic dysfunction. Answering whether or not these neuronal populations respond similarly in the setting of obesity or chronic heart failure (Patel & Zheng, 2012) will further advance and clarify the integral role these neurons play in health and disease. I look forward to future work that carries these findings and technical approaches further and continues to shed light on the important functional contribution of PVN neurons. No competing interests declared Sole author None." @default.
• W2896518745 created "2018-10-26" @default.
• W2896518745 creator A5058861880 @default.
• W2896518745 date "2018-10-23" @default.
• W2896518745 modified "2023-09-27" @default.
• W2896518745 title "Shining light on the paraventricular nucleus: the role of glutamatergic PVN neurons in blood pressure control" @default.
• W2896518745 cites W2093433413 @default.
• W2896518745 cites W2113191988 @default.
• W2896518745 cites W2143053439 @default.
• W2896518745 cites W2150852675 @default.
• W2896518745 cites W2890872081 @default.
• W2896518745 doi "https://doi.org/10.1113/jp277043" @default.
• W2896518745 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6292798" @default.
• W2896518745 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30300451" @default.
• W2896518745 hasPublicationYear "2018" @default.
• W2896518745 type Work @default.
• W2896518745 sameAs 2896518745 @default.
• W2896518745 citedByCount "4" @default.
• W2896518745 countsByYear W28965187452021 @default.
• W2896518745 countsByYear W28965187452022 @default.
• W2896518745 countsByYear W28965187452023 @default.
• W2896518745 crossrefType "journal-article" @default.
• W2896518745 hasAuthorship W2896518745A5058861880 @default.
• W2896518745 hasBestOaLocation W28965187451 @default.
• W2896518745 hasConcept C126322002 @default.
• W2896518745 hasConcept C134018914 @default.
• W2896518745 hasConcept C169760540 @default.
• W2896518745 hasConcept C170493617 @default.
• W2896518745 hasConcept C2776533406 @default.
• W2896518745 hasConcept C2777003273 @default.
• W2896518745 hasConcept C2780648746 @default.
• W2896518745 hasConcept C2908647359 @default.
• W2896518745 hasConcept C61174792 @default.
• W2896518745 hasConcept C71924100 @default.
• W2896518745 hasConcept C84393581 @default.
• W2896518745 hasConcept C86803240 @default.
• W2896518745 hasConcept C99454951 @default.
• W2896518745 hasConceptScore W2896518745C126322002 @default.
• W2896518745 hasConceptScore W2896518745C134018914 @default.
• W2896518745 hasConceptScore W2896518745C169760540 @default.
• W2896518745 hasConceptScore W2896518745C170493617 @default.
• W2896518745 hasConceptScore W2896518745C2776533406 @default.
• W2896518745 hasConceptScore W2896518745C2777003273 @default.
• W2896518745 hasConceptScore W2896518745C2780648746 @default.
• W2896518745 hasConceptScore W2896518745C2908647359 @default.
• W2896518745 hasConceptScore W2896518745C61174792 @default.
• W2896518745 hasConceptScore W2896518745C71924100 @default.
• W2896518745 hasConceptScore W2896518745C84393581 @default.
• W2896518745 hasConceptScore W2896518745C86803240 @default.
• W2896518745 hasConceptScore W2896518745C99454951 @default.
• W2896518745 hasIssue "24" @default.
• W2896518745 hasLocation W28965187451 @default.
• W2896518745 hasLocation W28965187452 @default.
• W2896518745 hasLocation W28965187453 @default.
• W2896518745 hasOpenAccess W2896518745 @default.
• W2896518745 hasPrimaryLocation W28965187451 @default.
• W2896518745 hasRelatedWork W2037487060 @default.
• W2896518745 hasRelatedWork W2051488242 @default.
• W2896518745 hasRelatedWork W2056116732 @default.
• W2896518745 hasRelatedWork W2066173879 @default.
• W2896518745 hasRelatedWork W2070793461 @default.
• W2896518745 hasRelatedWork W2074115578 @default.
• W2896518745 hasRelatedWork W2084435836 @default.
• W2896518745 hasRelatedWork W2109029595 @default.
• W2896518745 hasRelatedWork W2471757216 @default.
• W2896518745 hasRelatedWork W2773858965 @default.
• W2896518745 hasVolume "596" @default.
• W2896518745 isParatext "false" @default.
• W2896518745 isRetracted "false" @default.
• W2896518745 magId "2896518745" @default.
• W2896518745 workType "article" @default.